ABCA1 Is Coordinated with ABCB1 in the Arsenic-Resistance of Human Cells

Abstract

Arsenic is one of the most widespread global environmental toxicants associated with endemic poisoning. ATP-binding cassette (ABC) proteins are transmembrane channels that transport and dispose of lipids and metabolic products across the plasma membrane. The majority of ABC family members (including ABCB1 and ABCC1) are reported to play a role in the development of arsenic and drug resistance in mammals. Previously, we established a human arsenic-resistant ECV-304 (AsRE) cell line and identified ABCA1 as a novel arsenic resistance gene. In the current study, we further investigated the potential contribution of ABCA1, ABCB1, and ABCC1 to arsenic resistance through measurement of survival rates and arsenic accumulation in AsRE cells with RNA interference. The arsenic resistance capacity of ABCC1 was the strongest among the three genes, while those of ABCA1 and ABCB1 were similar. Double or triple gene knockdown of ABCA1, ABCB1, and ABCC1 via RNA interference led to a decrease significant in arsenic resistance when ABCA1/ABCB1 or ABCB1/ABCC1 were simultaneously silenced. Interestingly, no differences were evident between cells with ABCA1/ABCC1 and ABCC1 only knockdown. Our findings suggest that ABCA1 and ABCB1 proteins display similar arsenic resistance capabilities and possibly coordinate to promote arsenic resistance in AsRE cells.

Notes

Author Contributions

L.Y. and X.H.T. conceived and designed the experiments; T.Z. and W.Q.N. performed the experiments; Z.Y. and S.L.G. analyzed the data; C.H.D. contributed reagents/materials/analysis tools; X.L.X. wrote the paper. Authorship must be limited to those who have contributed substantially to the work reported.

Funding information

This work is supported by grants from National Natural Science Foundation of China (30560129) to L.Y., National Natural Science Foundation of China (31400630 and 31570738) to X.L.X., and National Natural Science Foundation of China (81772168) to X.H.T.